Immunoregulatory profiles in liver transplant recipients on different immunosuppressive agents

Josh Levitsky; Joshua Miller; Edward Wang; Anne Rosen; Cathy Flaa; Michael Abecassis; James Mathew; Anat Tambur

doi:10.1016/j.humimm.2008.12.008

Immunoregulatory profiles in liver transplant recipients on different immunosuppressive agents

Josh Levitsky, Joshua Miller, Edward Wang, Anne Rosen, Cathy Flaa, Michael Abecassis, James Mathew, Anat Tambur

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

We compared peripheral blood immunophenotyping in 31 adult liver transplant recipients on differing long-term immunosuppressive (IS) monotherapy with and without peri-transplantation alemtuzumab (AL) induction. All patients had been stable on monotherapy with either sirolimus (SRL) (n = 10) or without SRL (tacrolimus (TAC) (n = 10), mycophenolate mofetil (MMF) (n = 11)) for more than 6 months. Five-color flow cytometry for putative "regulatory" T and dendritic cells as well as serum assays for soluble HLA-G (sHLA-G) were performed. The SRL monotherapy group had significantly higher percentages of CD4+CD25^high+Foxp3+ T cells (1.3 ± 1.0) compared with the non-SRL group (0.7 ± 0.6) (p = 0.04). The SRL effect was even higher in a subset with prior AL induction and no prior hepatitis C or rejection (1.7 ± 0.2) compared with all other subgroups (0.7 ± 0.6) (p = 0.02). TAC patients showed significantly higher "regulatory" DC2:DC1 ratios (10 ± 7.6) compared with non-TAC patients (4.1 ± 2.3) (p = 0.04). Although sHLA-G levels appeared higher in TAC patients, the differences were not statistically significant. In conclusion, IS monotherapy provides an opportunity to investigate regulatory roles of individual agents. SRL maintenance and prior AL induction in subsets of patients appeared to show a regulatory T cell immunophenotype. However, TAC patients may have other regulatory characteristics, supporting the need for larger, prospective studies to clarify differences.

Original language	English (US)
Pages (from-to)	146-150
Number of pages	5
Journal	Human Immunology
Volume	70
Issue number	3
DOIs	https://doi.org/10.1016/j.humimm.2008.12.008
State	Published - Mar 2009
Externally published	Yes

Keywords

Dendritic cells
Immunophenotyping
Immunosuppression
Liver transplantation
Regulatory T cells

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.humimm.2008.12.008

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title = "Immunoregulatory profiles in liver transplant recipients on different immunosuppressive agents",

abstract = "We compared peripheral blood immunophenotyping in 31 adult liver transplant recipients on differing long-term immunosuppressive (IS) monotherapy with and without peri-transplantation alemtuzumab (AL) induction. All patients had been stable on monotherapy with either sirolimus (SRL) (n = 10) or without SRL (tacrolimus (TAC) (n = 10), mycophenolate mofetil (MMF) (n = 11)) for more than 6 months. Five-color flow cytometry for putative {"}regulatory{"} T and dendritic cells as well as serum assays for soluble HLA-G (sHLA-G) were performed. The SRL monotherapy group had significantly higher percentages of CD4+CD25high+Foxp3+ T cells (1.3 ± 1.0) compared with the non-SRL group (0.7 ± 0.6) (p = 0.04). The SRL effect was even higher in a subset with prior AL induction and no prior hepatitis C or rejection (1.7 ± 0.2) compared with all other subgroups (0.7 ± 0.6) (p = 0.02). TAC patients showed significantly higher {"}regulatory{"} DC2:DC1 ratios (10 ± 7.6) compared with non-TAC patients (4.1 ± 2.3) (p = 0.04). Although sHLA-G levels appeared higher in TAC patients, the differences were not statistically significant. In conclusion, IS monotherapy provides an opportunity to investigate regulatory roles of individual agents. SRL maintenance and prior AL induction in subsets of patients appeared to show a regulatory T cell immunophenotype. However, TAC patients may have other regulatory characteristics, supporting the need for larger, prospective studies to clarify differences.",

keywords = "Dendritic cells, Immunophenotyping, Immunosuppression, Liver transplantation, Regulatory T cells",

author = "Josh Levitsky and Joshua Miller and Edward Wang and Anne Rosen and Cathy Flaa and Michael Abecassis and James Mathew and Anat Tambur",

year = "2009",

month = mar,

doi = "10.1016/j.humimm.2008.12.008",

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pages = "146--150",

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T1 - Immunoregulatory profiles in liver transplant recipients on different immunosuppressive agents

AU - Levitsky, Josh

AU - Miller, Joshua

AU - Wang, Edward

AU - Rosen, Anne

AU - Flaa, Cathy

AU - Abecassis, Michael

AU - Mathew, James

AU - Tambur, Anat

PY - 2009/3

Y1 - 2009/3

N2 - We compared peripheral blood immunophenotyping in 31 adult liver transplant recipients on differing long-term immunosuppressive (IS) monotherapy with and without peri-transplantation alemtuzumab (AL) induction. All patients had been stable on monotherapy with either sirolimus (SRL) (n = 10) or without SRL (tacrolimus (TAC) (n = 10), mycophenolate mofetil (MMF) (n = 11)) for more than 6 months. Five-color flow cytometry for putative "regulatory" T and dendritic cells as well as serum assays for soluble HLA-G (sHLA-G) were performed. The SRL monotherapy group had significantly higher percentages of CD4+CD25high+Foxp3+ T cells (1.3 ± 1.0) compared with the non-SRL group (0.7 ± 0.6) (p = 0.04). The SRL effect was even higher in a subset with prior AL induction and no prior hepatitis C or rejection (1.7 ± 0.2) compared with all other subgroups (0.7 ± 0.6) (p = 0.02). TAC patients showed significantly higher "regulatory" DC2:DC1 ratios (10 ± 7.6) compared with non-TAC patients (4.1 ± 2.3) (p = 0.04). Although sHLA-G levels appeared higher in TAC patients, the differences were not statistically significant. In conclusion, IS monotherapy provides an opportunity to investigate regulatory roles of individual agents. SRL maintenance and prior AL induction in subsets of patients appeared to show a regulatory T cell immunophenotype. However, TAC patients may have other regulatory characteristics, supporting the need for larger, prospective studies to clarify differences.

AB - We compared peripheral blood immunophenotyping in 31 adult liver transplant recipients on differing long-term immunosuppressive (IS) monotherapy with and without peri-transplantation alemtuzumab (AL) induction. All patients had been stable on monotherapy with either sirolimus (SRL) (n = 10) or without SRL (tacrolimus (TAC) (n = 10), mycophenolate mofetil (MMF) (n = 11)) for more than 6 months. Five-color flow cytometry for putative "regulatory" T and dendritic cells as well as serum assays for soluble HLA-G (sHLA-G) were performed. The SRL monotherapy group had significantly higher percentages of CD4+CD25high+Foxp3+ T cells (1.3 ± 1.0) compared with the non-SRL group (0.7 ± 0.6) (p = 0.04). The SRL effect was even higher in a subset with prior AL induction and no prior hepatitis C or rejection (1.7 ± 0.2) compared with all other subgroups (0.7 ± 0.6) (p = 0.02). TAC patients showed significantly higher "regulatory" DC2:DC1 ratios (10 ± 7.6) compared with non-TAC patients (4.1 ± 2.3) (p = 0.04). Although sHLA-G levels appeared higher in TAC patients, the differences were not statistically significant. In conclusion, IS monotherapy provides an opportunity to investigate regulatory roles of individual agents. SRL maintenance and prior AL induction in subsets of patients appeared to show a regulatory T cell immunophenotype. However, TAC patients may have other regulatory characteristics, supporting the need for larger, prospective studies to clarify differences.

KW - Dendritic cells

KW - Immunophenotyping

KW - Immunosuppression

KW - Liver transplantation

KW - Regulatory T cells

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SP - 146

EP - 150

JO - Human Immunology

JF - Human Immunology

IS - 3

ER -

Immunoregulatory profiles in liver transplant recipients on different immunosuppressive agents

Abstract

Keywords

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